Compound having affinity substance to antibody and bioorthogonal functional group, or salt thereof

Abstract

Compounds having an affinity substance to an antibody and a bioorthogonal functional group, represented by the following Formula (I):whereinA is an affinity substance to an antibody,L is a divalent group comprising a leaving group,E is a divalent group comprising an electrophilic group (i) coupled with the leaving group and (ii) having ability to react with a nucleophilic group in the antibody,B is a bioorthogonal functional group, andthe leaving group has ability to be cleaved and eliminated from E by a reaction between the nucleophilic group and the electrophilic group, or a salt thereof, and the like are useful for labelling antibodies.

1 - 21 . (canceled) 
     
     
         22 . A compound having an affinity peptide to an antibody and a functional substance, represented by the following Formula (IV): 
       
         
           
           
               
               
           
         
         wherein 
         A is an affinity peptide having ability to bind to an Fc region of an antibody, wherein the affinity peptide has 10 to 40 amino acid residues, 
         L is a divalent group comprising a leaving group, wherein the leaving group is —S— or —O—, 
         E is a divalent group consisting of (a) an electrophilic group coupled with the leaving group and (b) a linear divalent group, and E is free of a peptide portion, 
         wherein the electrophilic group is —C(═O)—, and 
         wherein the linear divalent group is a linear divalent hydrocarbon group, —NH—, —O—, —C(═O)—, or a group consisting of a combination of 2 to 4 of these, and 
         F is a functional substance, wherein the functional substance is a drug, a labelling substance, or a stabilizer, 
         wherein the leaving group has ability to be cleaved and eliminated from E by a reaction between a nucleophilic group in the antibody and the electrophilic group, and 
         wherein the nucleophilic group is an amino group in a side chain of a lysine residue present in a constant region of the antibody, wherein the lysine residue is a lysine residue at positions 246 to 248 or 288 to 290 following Eu numbering in an antibody Fc, or 
         a salt thereof. 
       
     
     
         23 . The compound or salt thereof according to  claim 22 , wherein the linear divalent group is a group consisting of a combination of (i) a linear divalent hydrocarbon group and (ii) a group selected from the group consisting of —O— and —C(═O)—. 
     
     
         24 . The compound or salt thereof according to  claim 22 , wherein the linear divalent hydrocarbon group is linear alkylene, arylene, or a group consisting of a combination of these. 
     
     
         25 . The compound or salt thereof according to  claim 24 , wherein the linear alkylene is C1-12 linear alkylene. 
     
     
         26 . The compound or salt thereof according to  claim 24 , wherein the linear alkylene is C1-6 linear alkylene. 
     
     
         27 . The compound or salt thereof according to  claim 24 , wherein the linear alkylene is C1-4 linear alkylene. 
     
     
         28 . The compound or salt thereof according to  claim 22 , wherein the antibody is IgG. 
     
     
         29 . The compound or salt thereof according to  claim 22 , wherein the IgG is human IgG. 
     
     
         30 . The compound or salt thereof according to  claim 22 , wherein the functional substance is a substance that is derivatized from a drug, a labelling substance, or a stabilizer. 
     
     
         31 . A reagent of regioselectively modifying an antibody by a functional substance, the reagent comprising the compound or salt thereof according to  claim 22 . 
     
     
         32 . A method for producing an antibody having a functional substance or functional substances, or a salt thereof, the method comprising
 reacting the compound or salt thereof according to  claim 22  with an antibody   to form the antibody having a functional substance or functional substances, represented by the following Formula (V):   
       
         
           
           
               
               
           
         
         wherein 
         Ab is an antibody, 
         E is a divalent group consisting of (a) an electrophilic group coupled with an amino group in a side chain of a lysine residue present in a constant region of the antibody and (b) a linear divalent group, and E is free of a peptide portion, 
         wherein the lysine residue present in the constant region of the antibody is a lysine residue at positions 246 to 248 or 288 to 290 following Eu numbering in an antibody Fc, 
         wherein the electrophilic group is —C(═O)—, and 
         wherein the linear divalent group is a linear divalent hydrocarbon group, —NH—, —O—, —C(═O)—, or a group consisting of a combination of 2 to 4 of these, and 
         F is the same as that in the above Formula (IV), or a salt thereof.